Mercury compound of meta cresol



Patented Nov. 18, 1930 TE-D Z TA E sP EjNT;

1,782,090 I rr cj DUNCAN MACDONALD COPLEY AND JOHN PAUL sNYDEa, or nonwicrr, NEW YORK, As-

srenons TO THENORWICH PHARMAGAL COMPANY, onnonwicn, NEW aroma-11 CORPORATION NEW YORK MERCURY COMPOUND on META cREsoL No Drawing. v

The object of our invention is the production of an antiseptic and germicide of marked activity and power as such; and, more particularly, such a gerinioide containing a mercury compound. i i V W Further objects are the production of such a mercury compound which is usable medici-' nally and miscible with diluent and ointment vehicles for external and internal application; and which is'of low toxicity, highly pentrative, and not obj ectionably irritating to the membranes, skin and tissues of the body; and which, chemically considered, is of high mercury content, stable, odorless and colorless.

Our composition consists of thereaction products resultantfrom the mixture of a mercury compound withfa'n isomer 'OIVISOIDQIS of cresol, and preferably of a mercuric salt with meta ,cresol, by the "process whose steps are next hereinafter set forth. i v p v In; preparing our composition, we prefer to use the named ingredients in about the stated proportions, and to cause their chemi-,

cal combination and reaction by the method recited, since the bestresults have been secured by use of such materials in the quan: tities specified and'byour process, but this recital is intended merely by way of example illustrative'of the inventionand is not to be understoodas limiting our invention thereto.

In order to eXemplifythe materials and 7 process: p r Step J.Dissolve 21 grams of potassium hydroxide 'KOH in 150 cc. of specially denatured alcohol-No, 30, ire. U. S. Govern z intent-standard special denatured alcohol No.

' 30, (whose formula is statedtoybe 100 gals ethyl alcohol mixed with gals. methylalcohol) hereinafter referred to as alcohol No. 30. Filter the solution into, T05. grams' of meta cresol C HACHQ (OI-I) flRinse the filter with 25 cc. ofalcohol No. 30, andadd the rinsings to the filtration productl,

Step2.DissolVe 50.55 grams ofmercuric chloride, HgGl 111,300 ccfioflaloohol No,

Filter the solution, rinsing, the filterwith 25 I 00-0f alcohol No. 30and adding theyr'insings to the filtrationproduct.

Step'3.Add the solution resultant from v i i step 2 slowly to'the solution resultant from step 1, atroom temperature,'meanwhile constantlystirring the ingredients, Place the mixture upon a steam bath and allow to but soluble in dilute Application filed September 14:]19271 ser ai 532 15,558; a a

stand on the bath until the' precipitate depos ited becomes cream whitejinr-color and until the mixture hasconcentrated to a consistency at which it will just flow."

The product" as finished consists of 48.8 i

grams of anodorless, nearly white powder, 3

insoluble in'water, alcohol and, cold dilute hydrochloric acid or cold dilute nitric acid,

potassium or sodium,

hydroxide solution; 7

' This product, assayed by theelectrolytic Y e method, yields 67.87% metallic'mercury.

' A solution of the product obtained by dis SOlViIig Lgram of product'in 16 cc: of 9,10%

potassium hydroxide" solution and sufii'cient distilledwater'to'make 500 cc., (ifje, 1 to 5001) I may the inner anliydride 0f iiyamg was colorless andnearly clear,- becoming clear mercuri-meta-cresol,whose graphic formula I -.namely, the anginan o fhydr dxy er-f curi-meta-cresol (CgH (GH )HgO) but con-'- taining chloromercuri-meta-cresol and ,chloromercuri anhydrohydroxymercuric meta-cresol (C H (CH )HgO) HgCl), the same being entirely free from chlorine and from inorganic chlorideseMeta cresol is vchosen by way of preferentialillustration because it is believed to have the highest value in: bactericidal, activity of the three isomeric anodificationsbf cresol; 1 V v The cresol specified by theUnited States resultfasto product,a's'illustrated by the folture of the three cresol isomers.-

Dissolve 33.7 grams of mercuric chloride in continued agitation.

lowing exemplification:

Dissolve '14 grams of potassium hydroxide in special denatured alcohol "No. and add to 47 grams of cresol (U. SLR), i. e. a mixalcohol No. '80. Add the solution of mercuric chloride slowly to the cresol solution with i A yellow precipitate results which duringthirty minutes digestion upon the; steam bath becomes cream white incolor. Remove the potassium chloride by washing the precipitate upon a suction filter with a mixture of equalgparts of alcohol No. and distilled water.' "Collect the filtered and washed precipitate and rewash with undiluted alcohol 'No. 30 with heat for afew minutes, in order to remove the water left by the prior washing." Again drain the precipitate on the 'suctionfilter, dry at a vlow;temperature, and powder. The resultant product is a cream white pOWdenQpract'iCally odorless, insoluble in water, alcohol and d1,-

lute hydrochloric acid, but readily soluble in dilute potassium hydroxide solution. 'This precipitate represents the reaction product: .of ortho, metaand para cresol with mercuric. chloride, andis beheved'to be the hydroxymercuri substitutionproduct of the cresol isomers.

vA one to one hundred dilution of this prod- V uctin an ointment base composed of 7 5% petrolatum and 25% oleosteari'n shows aevery marked antiseptic activity when tested by the Reddish method for determining meanitled Drug Markets,at page 495 of, the

fissue dated May 31,1927; 3

TheReddish methodfreferred a is that Q i devised by Dr. Reddish and used in the Bureau of Chemistry of the U. S. Department y-"of Agriculture, and consists n coating a Pe trie dish with1 %agar, seeding the coating with staphlococci, spotting with the ointment to be observed, and incubating for .l8hoursat37G,

Under this test, mercuric chloride a positive result in dilutions of 1 to 2000 and and a discernible result in dilutions of 1 to 3000. ll iththe product of ourExample 1, mercurous salt of meta cresol, the like Reddish test gives a positive result in dilutions of l to 150,000, and a discernible result in dilutions of 1 to 200,000. V i i The products of both Examples 1 andQ show a bacteriostatic potency twice that 'of bichloride of mercury (HgGl ),'inequal ratios of dilutionat-37 0., upon a strain of microccus' aureus, supplied by the Department of Agriculture. In doses of 8 milligrams of our composition, Example No.1, per kilogram, of subject, injected intramuscular ly, our product was non-toxic; whereas a like quantity of mercuric chloride (HgCl simie larly administered was a lethal dose resulting in the death of the white rats thus treated.

In a weak potassium hydroxide dilution of 1 to 1500, both exampled products are nonirritant to-normal skin surfaces, when repeatedly applied to the same'area; and innocuous to throat membranes when applied Yin-1 to 3000 dilution, They are highly penetrative and do not coagulate with albumen as does mercuric chloride under the same conditions of'test. 1 Y

jlVhile we have thus described the utilities of the compositions'exampled as demonstrat ed by tests made by us, wealso believe that these organic mercury derivatives of meta cresol and of cresol mayfbe indicated with safety and benefit'forinte'rnal medication.

. We therefore claim as new and desire to secure by LettersPat ent':

' 1. The process of producing the organic mercury derivatlves of a cresol isomer consisting in filtering into the isomer an alcohol solutionof potassium hydroxide, slowly adding thereto'an alcohol solution of a'mercuric salt, and meanwhile agitating the mixture,

then concentrating same and promoting rea'ction by low heat, cooling, filtering,.and'washing' until ,onlyvery' faint traces of chlorides appear, andfi'nally drying same.

2.- The processof producing orga-nic mercury der vatlves'of meta-cresol consisting in filtering into'theisomer an alcohol solution of potassium hydroxide, slowly adding there- 7 to an"alcoliol' solution of mercuric chloride,

and meanwhile agitating the mixture, then 7 tiseptic'rproperties of ointments. Of. the article by George F. Reddishin thepublication of potassium hydroxide, slowly adding there to an alcohol solution of a soluble mercuric salt, meanwhile agitating the mixture; con

hydroxy mercuric meta-cresol.

5. Ant antiseptic andgermicidal composi-' tion containing the inner anhydride of hyn droxymercuri meta-cresol and. chloromer V curi-meta-cresol and 'chloromercuri-anhydrohydroxy mercuric m'eta-cresol, the same being entirely free from chlorine and from inorganic chlorides. V v

6. An antiseptic and germicidal composition consistingof the hydromercuri substitution product of a mixture'of a plurality of cresol isomers, one of which is meta-cresol, Withmercuric chloride, the said product being 'a cream White powder,'substantially odorless, and insoluble in'water, alcohol and cold dilutehydrochloric acidoor cold dilute nitric acid; but readily soluble indilute potassiumhydroxide solution or sodium-hydroxide solution; the same being entirely free from chlorine and from inorganic chlorides, and containing about 68 per cent. metallic mercury and having a bacteriostatic potency twice that ofbichloride of mercury in equal ratios of dilution. 1

DUNOAN MAODONALD COPLEY.

JOHN PAUL SNYDER.

chloromer curi-meta-cresol and chloromercuri-anhydro- 

